0 10 Inhibition Inhibition NNP 11 13 of of IN 14 19 NF-AT NF-AT NNP 20 26 signal signal NN 27 39 transduction transduction NN 40 46 events event NNS 47 49 by by IN 50 51 a a DT 52 69 dominant-negative dominant-negative JJ 70 74 form form NN 75 77 of of IN 78 89 calcineurin calcineurin NN 89 90 . . . 92 94 An an DT 95 105 inhibitory inhibitory JJ 105 106 , , , 107 108 “ `` `` 108 125 dominant-negative dominant-negative JJ 125 126 , , , 126 127 ” '' '' 128 132 form form NN 133 135 of of IN 136 139 the the DT 140 151 calcineurin calcineurin NN 152 161 catalytic catalytic JJ 162 163 ( ( ( 163 164 A a NN 164 165 ) ) ) 166 173 subunit subunit NN 174 177 was be VBD 178 186 prepared prepare VBN 186 187 , , , 188 193 which which WDT 194 199 lacks lack VBZ 200 203 the the DT 204 222 calmodulin-binding calmodulin-binding JJ 223 229 domain domain NN 229 230 , , , 231 245 autoinhibitory autoinhibitory JJ 246 252 domain domain NN 253 256 and and CC 257 261 most most JJS 262 264 of of IN 265 268 its its PRP$ 269 278 catalytic catalytic JJ 279 283 core core NN 284 287 but but CC 288 297 possesses possess VBZ 298 301 the the DT 302 312 regulatory regulatory JJ 313 314 ( ( ( 314 315 B B NNP 315 316 ) ) ) 317 324 subunit subunit NN 325 332 binding binding NN 333 339 domain domain NN 339 340 . . . 341 345 When when WRB 346 352 tested test VBN 353 356 for for IN 357 360 its its PRP$ 361 368 ability ability NN 369 371 to to TO 372 377 block block VB 378 399 calcineurin-dependent calcineurin-dependent JJ 400 409 signaling signaling NN 410 412 in in IN 413 419 Jurkat Jurkat NNP 420 425 cells cell NNS 425 426 , , , 427 437 expression expression NN 438 440 of of IN 441 445 this this DT 446 447 “ `` `` 447 456 B-subunit b-subunit NN 457 466 knock-out knock-out JJ 466 467 ” '' '' 468 469 ( ( ( 469 472 BKO BKO NNP 472 473 ) ) ) 474 483 construct construct NN 484 494 suppressed suppress VBD 495 503 reporter reporter NN 504 508 gene gene NN 509 517 activity activity NN 518 524 driven drive VBN 525 527 by by IN 528 533 NF-AT NF-AT NNP 533 534 , , , 535 538 the the DT 539 546 pivotal pivotal JJ 547 555 promoter promoter NN 556 563 element element NN 564 567 for for IN 568 579 interleukin interleukin NN 580 581 ( ( ( 581 586 IL)-2 il)-2 NN 587 591 gene gene NN 592 601 induction induction NN 601 602 . . . 603 622 Immunoprecipitation Immunoprecipitation NNP 623 625 of of IN 626 641 epitope-labeled epitope-labeled JJ 642 645 BKO bko NN 646 658 demonstrated demonstrate VBD 659 662 for for IN 663 666 the the DT 667 676 formation formation NN 677 679 of of IN 680 681 a a DT 682 687 tight tight JJ 688 695 complex complex NN 696 700 with with IN 701 711 endogenous endogenous JJ 712 713 B B NNP 714 721 subunit subunit NN 722 724 in in IN 725 731 Jurkat Jurkat NNP 732 737 cells cell NNS 737 738 , , , 739 749 consistent consistent JJ 750 754 with with IN 755 757 an an DT 758 768 inhibitory inhibitory JJ 769 778 mechanism mechanism NN 779 783 that that WDT 784 792 involves involve VBZ 793 796 the the DT 797 810 sequestration sequestration NN 811 813 of of IN 814 817 the the DT 818 819 B B NNP 820 827 subunit subunit NN 827 828 . . . 829 840 Furthermore furthermore RB 840 841 , , , 842 845 the the DT 846 853 sharply sharply RB 854 861 reduced reduce VBN 862 867 NF-AT NF-AT NNP 868 876 activity activity NN 877 885 produced produce VBN 886 888 by by IN 889 904 co-transfecting co-transfecte VBG 905 908 BKO BKO NNP 909 914 could could MD 915 917 be be VB 918 919 “ `` `` 919 926 rescued rescue VBN 926 927 ” '' '' 928 930 by by IN 931 945 overexpression overexpression NN 946 948 of of IN 949 960 transfected transfecte VBN 961 962 B B NNP 963 970 subunit subunit NN 970 971 , , , 972 982 suggesting suggest VBG 983 987 that that IN 988 997 depletion depletion NN 998 1000 of of IN 1001 1005 this this DT 1006 1013 subunit subunit NN 1014 1017 was be VBD 1018 1029 responsible responsible JJ 1030 1033 for for IN 1034 1037 the the DT 1038 1048 inhibition inhibition NN 1048 1049 . . . 1050 1055 These these DT 1056 1060 data datum NNS 1061 1068 suggest suggest VBP 1069 1072 the the DT 1073 1082 potential potential JJ 1083 1090 utility utility NN 1091 1093 of of IN 1094 1100 agents agent NNS 1101 1105 that that WDT 1106 1113 disrupt disrupt VBP 1114 1134 calcineurin-mediated calcineurin-mediated JJ 1135 1141 signal signal NN 1142 1154 transduction transduction NN 1155 1163 pathways pathway NNS 1164 1166 by by IN 1167 1175 blocking block VBG 1176 1185 formation formation NN 1186 1188 of of IN 1189 1192 the the DT 1193 1206 catalytically catalytically RB 1207 1213 active active JJ 1214 1219 dimer dimer NN 1220 1222 of of IN 1223 1234 calcineurin calcineurin NN 1235 1236 A A NNP 1237 1240 and and CC 1241 1242 B B NNP 1243 1251 subunits subunit NNS 1251 1252 . . .